Innovative therapies for acute bacterial skin and skin-structure infections (ABSSSI) caused by methicillin-resistant Staphylococcus aureus: advances in phase I and II trials

References

• Russo A, Concia E, Cristini F, et al. Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections. Clin Microbiol Infect. 2016;22(Suppl 2):S27–36. .
   PubMed Web of Science ®Google Scholar
• Esposito S, Noviello S, Leone S. Epidemiology and microbiology of skin and soft tissue infections. Curr Opin Infect Dis. 2016;29(2):109–115.
   PubMed Web of Science ®Google Scholar
• Miller LG, Eisenberg DF, Liu H, et al. Incidence of skin and soft tissue infections in ambulatory and inpatient settings, 2005–2010. BMC Infect Dis. 2015;15(1):362. .
   PubMedGoogle Scholar
• Edelsberg J, Taneja C, Zervos M, et al., Trends in US hospital admissions for skin and soft tissue infections. Emerg Infect Dis. 2009;15(9): 1516–1518. .
   PubMed Web of Science ®Google Scholar
• Garau J, Ostermann H, Medina J, et al. Current management of patients hospitalized with complicated skin and soft tissue infections across Europe (2010–2011): assessment of clinical practice patterns and real-life effectiveness of antibiotics from the REACH study. Clin Microbiol Infect. 2013;19(9):E377–385. .
   PubMed Web of Science ®Google Scholar
• Hersh AL, Chambers HF, Maselli JH, et al. National trends in ambulatory visits and antibiotic prescribing for skin and soft-tissue infections. Arch Intern Med. 2008;168(14):1585–1591.
   PubMed Web of Science ®Google Scholar
• Kaye KS, Patel DA, Stephens JM, et al. Rising United States hospital admissions for acute bacterial skin and skin structure infections: recent trends and economic impact. PLoS One. 2015;10(11):e0143276. .
   PubMed Web of Science ®Google Scholar
• Kaye KS, Petty LA, Shorr AF, et al. Current epidemiology, etiology, and burden of acute skin infections in the United States. Clin Infect Dis. 2019;68(Supplement_3):S193–S199.
   PubMedGoogle Scholar
• Morgan E, Hohmann S, Ridgway JP, et al. Decreasing incidence of skin and soft-tissue infections in 86 US emergency departments, 2009–2014. Clin Infect Dis. 2019;68(3):453–459. .
   PubMed Web of Science ®Google Scholar
• Ray GT, Suaya JA, Baxter R. Incidence, microbiology, and patient characteristics of skin and soft-tissue infections in a U.S. population: a retrospective population-based study. BMC Infect Dis. 2013;13(1):252.
   PubMedGoogle Scholar
• Lagi F, Ottino L, Mantengoli E, et al. Early discharge criteria in patients with acute bacterial skin and skin structure infections in a large tertiary-care teaching hospital in Florence, Italy. Eur J Clin Microbiol Infect Dis. 2019;38(9):1781–1785. .
   PubMed Web of Science ®Google Scholar
• Sader HS, Streit JM, Carvalhaes CG, et al. Frequency and antimicrobial susceptibility of bacterial isolates from patients hospitalised with community-acquired skin and skin-structure infection in Europe, Asia and Latin America. J Glob Antimicrob Resist. 2019;17:103–108.
   PubMed Web of Science ®Google Scholar
• Livermore DM, Mushtaq S, Warner M, et al. Pathogens of skin and skin-structure infections in the UK and their susceptibility to antibiotics, including ceftaroline. J Antimicrob Chemother. 2015;70(10):2844–2853. .
   PubMed Web of Science ®Google Scholar
• Labreche MJ, Lee GC, Attridge RT, et al. Treatment failure and costs in patients with methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections: a South Texas Ambulatory Research Network (STARNet) study. J Am Board Fam Med. 2013;26:508–517.
   PubMed Web of Science ®Google Scholar
• Moran GJ, Abrahamian FM, Lovecchio F, et al. Acute bacterial skin infections: developments since the 2005 infectious diseases society of America (IDSA) guidelines. J Emerg Med. 2013;44(6):e397–412.
   PubMedGoogle Scholar
• Pulido-Cejudo A, Guzman-Gutierrez M, Jalife-Montano A, et al. Management of acute bacterial skin and skin structure infections with a focus on patients at high risk of treatment failure. Ther Adv Infect Dis. 2017;4(5):143–161. .
   PubMed Web of Science ®Google Scholar
• Kowalski RP, Romanowski EG, Yates KA, et al. An independent evaluation of a novel peptide mimetic, Brilacidin (PMX30063), for ocular anti-infective. J Ocul Pharmacol Ther. 2016;32(1):23–27.
   PubMed Web of Science ®Google Scholar
• Mensa B, Howell GL, Scott R, et al. Comparative mechanistic studies of brilacidin, daptomycin, and the antimicrobial peptide LL16. Antimicrob Agents Chemother. 2014;58(9):5136–5145.
   PubMed Web of Science ®Google Scholar
• Scott RW, Sonis ST, Korczak B, et al. Brilacidin, host defence peptide mimetic, one of a new class of immunomodulatory agents that can target multiple disease indications. Presented at: 25th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), April 25-28, 2015, Copenhagen, Denmark.
   Google Scholar
• Jorgensen DM, Scott RW, O’Riordan WA, et al. A randomized, double-blind study comparing single-dose and short-course brilacidin to daptomycin in the treatment of acute bacterial skin & skin structure infections (ABSSSI). Presented at: 25th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), April 25-28, 2015, Copenhagen, Denmark.
   Google Scholar
• Innovation Pharmaceuticals Inc. Cellceutix to start brilacidin phase 3 program in ABSSSI [cited 2019 Oct 24]. Available from: http://www.ipharminc.com/press-release/2016/11/16/cellceutix-to-start-brilacidin-phase-3-program-in-absssi.
   Google Scholar
• 10-Q: Press release. Innovation Pharmaceuticals Inc [cited 2019 Oct 23]. Available from: https://www.marketwatch.com/press-release/10-q-innovation-pharmaceuticals-inc-2018-11-08.
   Google Scholar
• Innovation Pharmaceuticals Inc. Innovation pharmaceuticals clinical trial of oral brilacidin in ulcerative colitis program expected to commence in December. [cited 2019 Oct 23]. Available from: http://www.ipharminc.com/press-release/2019/10/3/innovation-pharmaceuticals-clinical-trial-of-oral-brilacidin-in-ulcerative-colitis-program-expected-to-commence-in-december-top-line-data-in-q1-2020.
   Google Scholar
• Dillon C, Guarascio AJ, Covvey JR. Lefamulin: a promising new pleuromutilin antibiotic in the pipeline. Expert Rev Anti Infect Ther. 2019;17(1):5–15.
   PubMed Web of Science ®Google Scholar
• Veve MP, Wagner JL. Lefamulin: review of a promising novel pleuromutilin antibiotic. Pharmacotherapy. 2018;38(9):935–946.
   PubMed Web of Science ®Google Scholar
• Sader HS, Biedenbach DJ, Paukner S, et al. Antimicrobial activity of the investigational pleuromutilin compound BC-3781 tested against Gram-positive organisms commonly associated with acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2012;56(3):1619–1623. .
   PubMed Web of Science ®Google Scholar
• Sader HS, Paukner S, Ivezic-Schoenfeld Z, et al. Antimicrobial activity of the novel pleuromutilin antibiotic BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs). J Antimicrob Chemother. 2012;67(5):1170–1175.
   PubMed Web of Science ®Google Scholar
• Alexander E, Goldberg L, Das AF, et al. Oral lefamulin vs moxifloxacin for early clinical response among adults with community-acquired bacterial pneumonia: the LEAP 2 randomized clinical trial. JAMA. 2019;322(17):1661.
   Web of Science ®Google Scholar
• File TM Jr., Goldberg L, Das A, et al. Efficacy and safety of IV-to-oral lefamulin, a pleuromutilin antibiotic, for treatment of community-acquired bacterial pneumonia: the phase 3 LEAP 1 trial. Clin Infect Dis. 2019;69(11):1856–1867. .
   Web of Science ®Google Scholar
• Prince WT, Ivezic-Schoenfeld Z, Lell C, et al. Phase II clinical study of BC-3781, a pleuromutilin antibiotic, in treatment of patients with acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2013;57(5):2087–2094. .
   PubMed Web of Science ®Google Scholar
• Nabriva therapeutics. pipeline & research [cited 2019 Oct 24]. Available from: https://www.nabriva.com/pipeline-research.
   Google Scholar
• Flamm RK, Rhomberg PR, Kaplan N, et al. Activity of Debio1452, a FabI inhibitor with potent activity against Staphylococcus aureus and coagulase-negative Staphylococcus spp., including multidrug-resistant strains. Antimicrob Agents Chemother. 2015;59:2583–2587.
   PubMed Web of Science ®Google Scholar
• Menetrey A, Janin A, Pullman J, et al. Bone and joint tissue penetration of the staphylococcus-selective antibiotic afabicin in patients undergoing elective hip replacement surgery. Antimicrob Agents Chemother. 2019;63(8). DOI:10.1128/AAC.00779-19.
   PubMedGoogle Scholar
• DebiopharmGroup. Debiopharm international SA announces positive phase 2 clinical trial with Debio 1450 in ABSSSI patients [cited 2019 Oct 24]. Available from: https://www.debiopharm.com/debiopharm-international/press-releases/debiopharm-international-sa-announces-positive-phase-2-clinical-trial-with-debio-1450-in-absssi-patients/.
   Google Scholar
• Hafkin B, Kaplan N, Efficacy MB. Safety of AFN-1252, the first staphylococcus-specific antibacterial agent, in the treatment of acute bacterial skin and skin structure infections, including those in patients with significant comorbidities. Antimicrob Agents Chemother. 2015;60(3):1695–1701.
   PubMed Web of Science ®Google Scholar
• Kaplan N, Hafkin B Preclinical pharmacokinetics and efficacy of Debio 1450 (Previously AFN-1720), a prodrug of the Staphylococcocal-specific Antibiotic Debio 1452 (Previously AFN-1252). Presented at: 24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), May 10-13, 2014, Barcelona, Spain.
   Google Scholar
• Nowakowska J, Kuehn J, Vincent C, et al. Staphylococcal-selective antibiotic afabicin preserves the human gutmicrobiota. Presented at: 28th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), April 21-24, 2018, Madrid, Spain.
   Google Scholar
• Kim BY, Sohn YT. Solid state of CG-400549, a novel FabI inhibitor: characterization, dissolution, transformation. Arch Pharm Res. 2011;34(5):775–779.
   PubMed Web of Science ®Google Scholar
• Bogdanovich T, Clark C, Kosowska-Shick K, et al. Antistaphylococcal activity of CG400549, a new experimental FabI inhibitor, compared with that of other agents. Antimicrob Agents Chemother. 2007;51(11):4191–4195. .
   PubMed Web of Science ®Google Scholar
• Yum JH, Kim CK, Yong D, et al. In vitro activities of CG400549, a novel FabI inhibitor, against recently isolated clinical staphylococcal strains in Korea. Antimicrob Agents Chemother. 2007;51(7):2591–2593. .
   PubMed Web of Science ®Google Scholar
• CrystalGenomics, Inc. CrystalGenomics reports positive top-line data from phase 2a study of CG400549 in patients with complicated acute bacterial skin and skin structure infections caused by MRSA. [cited 2019 Oct 22]. Available from: https://www.prnewswire.com/news-releases/crystalgenomics-reports-positive-top-line-data-from-phase-2a-study-of-cg400549-in-patients-with-complicated-acute-bacterial-skin-and-skin-structure-infections-caused-by-mrsa-185870042.html.
   Google Scholar
• Jeong JW, Jung SJ, Lee HH, et al. In vitro and in vivo activities of LCB01-0371, a new oxazolidinone. Antimicrob Agents Chemother. 2010;54(12):5359–5362. .
   PubMed Web of Science ®Google Scholar
• Cho YS, Lim HS, Lee SH, et al. Pharmacokinetics, pharmacodynamics, and tolerability of single-dose oral LCB01-0371, a novel oxazolidinone with broad-spectrum activity, in healthy volunteers. Antimicrob Agents Chemother. 2018;62(7).
   Web of Science ®Google Scholar
• Cho YS, Lim HS, Cho YL, et al. Multiple-dose safety, tolerability, pharmacokinetics, and pharmacodynamics of oral LCB01-0371 in healthy male volunteers. Clin Ther. 2018;40(12):2050–2064. .
   PubMed Web of Science ®Google Scholar
• Choi Y, Lee SW, Kim A, et al. Safety, tolerability and pharmacokinetics of 21 day multiple oral administration of a new oxazolidinone antibiotic, LCB01-0371, in healthy male subjects. J Antimicrob Chemother. 2018;73(1):183–190. .
   PubMed Web of Science ®Google Scholar
• Cho YS, Lim HS, Han S, et al. Single-dose intravenous safety, tolerability, and pharmacokinetics and absolute bioavailability of LCB01-0371. Clin Ther. 2019;41(1):92–106. .
   PubMed Web of Science ®Google Scholar
• Bassetti M, Merelli M, Temperoni C, et al. New antibiotics for bad bugs: where are we? Ann Clin Microbiol Antimicrob. 2013;12(1):22.
   PubMed Web of Science ®Google Scholar
• Lemaire S, Kosowska-Shick K, Appelbaum PC, et al. Cellular pharmacodynamics of the novel biaryloxazolidinone radezolid: studies with infected phagocytic and nonphagocytic cells, using Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes, and Legionella pneumophila. Antimicrob Agents Chemother. 2010;54(6):2549–2559. .
   PubMed Web of Science ®Google Scholar
• Moellering RC Jr. Discovering new antimicrobial agents. Int J Antimicrob Agents. 2011;37(1):2–9.
   PubMed Web of Science ®Google Scholar
• Safety and efficacy study of oxazolidinones to treat uncomplicated skin infections. [cited 2019 Oct 23]. Available from: https://clinicaltrials.gov/ct2/show/results/NCT00646958.
   Google Scholar
• Melinta Therapeutics. Melinta Therapeutics’ topical radezolid well tolerated in phase I study for treatment of acne [cited 2019 Oct 23]. Available from: https://melinta.com/melinta-therapeutics-topical-radezolid-well-tolerated-phase-1-study-treatment-acne/.
   Google Scholar
• Li CR, Zhai QQ, Wang XK, et al. In vivo antibacterial activity of MRX-I, a new oxazolidinone. Antimicrob Agents Chemother. 2014;58(4):2418–2421. .
   PubMed Web of Science ®Google Scholar
• Bulitta J, Fang E, Atiee G, et al. Population pharmacokinetics of the new oxazolidinone prodrug contezolid acefosamil (MRX-4) and its metabolites after single and multiple ascending intravenous doses in healthy volunteers. Presented at: 29th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), April 13-16, 2019, Amsterdam, Netherlands.
   Google Scholar
• MicuRx Pharmaceuticals, Inc. MicuRx pharmaceuticals reports positive top-line results from a US Phase 2 ABSSSI clinical trial of novel antibiotic contezolid acefosamil. [cited 2019 Oct 24]. Available from: https://www.businesswire.com/news/home/20190909005015/en/.
   Google Scholar
• MicuRx Pharmaceuticals, Inc. MicuRX announces positive top-line results from phase 3 trial of contezolid (MRX-I) in adults with complicated skin and soft tissue infection. [cited 2019 Oct 24]. Available from: https://www.trialsitenews.com/micurx-announces-positive-topline-results-from-phase-3-trial-of-contezolid-mrx-i-in-adults-with-complicated-skin-and-soft-tissue-infection-2/.
   Google Scholar
• Rodvold KA, Gotfried MH, Chugh R, et al. Intrapulmonary pharmacokinetics of levonadifloxacin following oral administration of Alalevonadifloxacin to healthy adult subjects. Antimicrob Agents Chemother. 2018;62.
   Web of Science ®Google Scholar
• Tellis M, Joseph J, Khande H, et al. In vitro bactericidal activity of levonadifloxacin (WCK 771) against methicillin- and quinolone-resistant Staphylococcus aureus biofilms. J Med Microbiol. 2019;68(8):1129–1136. .
   PubMed Web of Science ®Google Scholar
• Patel MV, De Souza NJ, Gupte SV, et al. Antistaphylococcal activity of WCK 771, a tricyclic fluoroquinolone, in animal infection models. Antimicrob Agents Chemother. 2004;48(12):4754–4761. .
   PubMed Web of Science ®Google Scholar
• Bhagwat SS, McGhee P, Kosowska-Shick K, et al. In vitro activity of the quinolone WCK 771 against recent U.S. hospital and community-acquired Staphylococcus aureus pathogens with various resistance types. Antimicrob Agents Chemother. 2009;53(2):811–813. .
   PubMed Web of Science ®Google Scholar
• World Health Organization. Antibacterial agents in clinical development. An analysis of the antibacterial clinical development pipeline, including tuberculosis. [cited 2019 Oct 20]. Available from: https://apps.who.int/iris/bitstream/handle/10665/258965/WHO-EMP-IAU-2017.11-eng.pdf.
   Google Scholar
• Chugh R, Lakdavala F, Bhatia A Safety and pharmacokinetics of multiple ascending doses of WCK 771 and WCK 2349. [cited 2019 Oct 20]. Presented at: 26th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), April 12-16, 2016, Amsterdam, Netherlands.
   Google Scholar
• Mason JW, Chugh R, Patel A, et al. Electrocardiographic effects of a supratherapeutic dose of WCK 2349, a benzoquinolizine fluoroquinolone. Clin Transl Sci. 2019;12(1):47–52. .
   PubMed Web of Science ®Google Scholar
• Jones TM, Johnson SW, DiMondi VP, et al. Focus on JNJ-Q2, a novel fluoroquinolone, for the management of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. Infect Drug Resist. 2016;9:119–128.
   PubMed Web of Science ®Google Scholar
• Morrow BJ, Abbanat D, Baum EZ, et al. Antistaphylococcal activities of the new fluoroquinolone JNJ-Q2. Antimicrob Agents Chemother. 2011;55(12):5512–5521. .
   PubMed Web of Science ®Google Scholar
• Morrow BJ, He W, Amsler KM, et al. In vitro antibacterial activities of JNJ-Q2, a new broad-spectrum fluoroquinolone. Antimicrob Agents Chemother. 2010;54(5):1955–1964. .
   PubMed Web of Science ®Google Scholar
• Fernandez J, Hilliard JJ, Morrow BJ, et al. Efficacy of a new fluoroquinolone, JNJ-Q2, in murine models of Staphylococcus aureus and Streptococcus pneumoniae skin, respiratory, and systemic infections. Antimicrob Agents Chemother. 2011;55(12):5522–5528. .
   PubMed Web of Science ®Google Scholar
• Covington P, Davenport JM, Andrae D, et al. Randomized, double-blind, phase II, multicenter study evaluating the safety/tolerability and efficacy of JNJ-Q2, a novel fluoroquinolone, compared with linezolid for treatment of acute bacterial skin and skin structure infection. Antimicrob Agents Chemother. 2011;55(12):5790–5797. .
   PubMed Web of Science ®Google Scholar
• Eichenbaum G, Pugsley MK, Gallacher DJ, et al. Role of mixed ion channel effects in the cardiovascular safety assessment of the novel anti-MRSA fluoroquinolone JNJ-Q2. Br J Pharmacol. 2012;166(5):1694–1707. .
   PubMed Web of Science ®Google Scholar
• Kishii R, Yamaguchi Y, Takei M. In vitro activities and spectrum of the novel fluoroquinolone lascufloxacin (KRP-AM1977). Antimicrob Agents Chemother. 2017;61(6). DOI:10.1128/AAC.00120-17
   PubMed Web of Science ®Google Scholar
• Kocsis B, Domokos J, Szabo D. Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin. Ann Clin Microbiol Antimicrob. 2016;15(1):34.
   PubMedGoogle Scholar
• Righi E, Carnelutti A, Vena A, et al. Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin. Infect Drug Resist. 2018;11:479–488.
   PubMed Web of Science ®Google Scholar
• Ma Z, Lynch AS. Development of a dual-acting antibacterial agent (TNP-2092) for the treatment of persistent bacterial infections. J Med Chem. 2016;59(14):6645–6657.
   PubMed Web of Science ®Google Scholar
• Robertson GT, Bonventre EJ, Doyle TB, et al. In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus. Antimicrob Agents Chemother. 2008;52(7):2313–2323. .
   PubMed Web of Science ®Google Scholar
• Koné I, Zimmermann B, Wangmo T, et al. Hospital discharge of patients with ongoing care needs: a cross-sectional study using data from a city hospital under SwissDRG. Swiss Med Wkly. 2018;148:w14630.
   PubMed Web of Science ®Google Scholar
• Bax BD, Chan PF, Eggleston DS, et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature. 2010;466(7309):935–940. .
   PubMed Web of Science ®Google Scholar
• Bulik CC, Okusanya OO, Lakota EA, et al. Pharmacokinetic-pharmacodynamic evaluation of gepotidacin against gram-positive organisms using data from murine infection models. Antimicrob Agents Chemother. 2017;61.
   Google Scholar
• Biedenbach DJ, Bouchillon SK, Hackel M, et al. In vitro activity of gepotidacin, a novel triazaacenaphthylene bacterial topoisomerase inhibitor, against a broad spectrum of bacterial pathogens. Antimicrob Agents Chemother. 2016;60(3):1918–1923. .
   PubMed Web of Science ®Google Scholar
• Flamm RK, Farrell DJ, Rhomberg PR, et al. Gepotidacin (GSK2140944) in vitro activity against gram-positive and gram-negative bacteria. Antimicrob Agents Chemother. 2017;61(7). DOI:10.1128/AAC.00468-17.
   Web of Science ®Google Scholar
• Gibson EG, Bax B, Chan PF, et al. Mechanistic and structural basis for the actions of the antibacterial gepotidacin against Staphylococcus aureus Gyrase. ACS Infect Dis. 2019;5(4):570–581.
   PubMed Web of Science ®Google Scholar
• O’Riordan W, Tiffany C, Scangarella-Oman N, et al. Efficacy, safety, and tolerability of gepotidacin (GSK2140944) in the treatment of patients with suspected or confirmed gram-positive acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2017;61.
   Web of Science ®Google Scholar
• Hossain M, Zhou M, Tiffany C, et al. A phase i, randomized, double-blinded, placebo- and moxifloxacin-controlled, four-period crossover study to evaluate the effect of gepotidacin on cardiac conduction as assessed by 12-lead electrocardiogram in healthy volunteers. Antimicrob Agents Chemother. 2017;61.
   Web of Science ®Google Scholar
• Blais J, Lewis SR, Krause KM, et al. Antistaphylococcal activity of TD-1792, a multivalent glycopeptide-cephalosporin antibiotic. Antimicrob Agents Chemother. 2012;56(3):1584–1587.
   PubMed Web of Science ®Google Scholar
• Stryjewski ME, Potgieter PD, Li YP, et al. TD-1792 versus vancomycin for treatment of complicated skin and skin structure infections. Antimicrob Agents Chemother. 2012;56(11):5476–5483. .
   PubMed Web of Science ®Google Scholar
• R-Pharm. R-Pharm group of companies continues development of new generation antibiotic. [cited 2019 Oct 23]. Available from: http://www.r-pharm.com/en/press-center/news/197.
   Google Scholar
• Schuch R, Khan BK, Raz A, et al. Bacteriophage Lysin CF-301, a potent antistaphylococcal biofilm agent. Antimicrob Agents Chemother. 2017;61(7). DOI:10.1128/AAC.02666-16.
   PubMed Web of Science ®Google Scholar
• Traczewski M, Oh J, Cassino C, et al. In vitro activity of Exebacase (CF-301) against clinical Staphylococcus aureus surveillance isolates from the United States, Europe, and Latin America, 2015-2017. Diagn Microbiol Infect Dis. 2019;95(4):114879.
   PubMed Web of Science ®Google Scholar
• Karau MJ, Schmidt-Malan SM, Yan Q, et al. Exebacase in addition to daptomycin is more active than daptomycin or exebacase alone in methicillin-resistant Staphylococcus aureus Osteomyelitis in Rats. Antimicrob Agents Chemother. 2019;63(10). DOI:10.1128/AAC.01235-19.
   Web of Science ®Google Scholar
• Schuch R, Lee HM, Schneider BC, et al. Combination therapy with lysin CF-301 and antibiotic is superior to antibiotic alone for treating methicillin-resistant Staphylococcus aureus-induced murine bacteremia. J Infect Dis. 2014;209(9):1469–1478.
   PubMed Web of Science ®Google Scholar
• ContraFect Corporation. ContraFect’s exebacase (CF-301) improved clinical outcomes in Staphylococcus aureus bacteremia including right-sided endocarditis compared to standard of care antibiotics alone in a first-in-patient phase 2 superiority study. [cited 2019 Oct 22]. Available from: https://www.globenewswire.com/news-release/2019/01/07/1681122/0/en/ContraFect-s-Exebacase-CF-301-Improved-Clinical-Outcomes-in-Staphylococcus-aureus-Bacteremia-including-Right-Sided-Endocarditis-Compared-to-Standard-of-Care-Antibiotics-Alone-in-a-.html.
   Google Scholar
• ContraFect Corporation. ContraFect announces plan for a single phase 3 superiority design study of exebacase following successful end-of-phase 2 meeting with FDA. [cited 2019 Oct 22]. Available from: https://www.globenewswire.com/news-release/2019/10/02/1923936/0/en/ContraFect-Announces-Plan-for-a-Single-Phase-3-Superiority-Design-Study-of-Exebacase-Following-Successful-End-of-Phase-2-Meeting-with-FDA.html.
   Google Scholar
• Jun SY, Jung GM, Yoon SJ, et al. Antibacterial properties of a pre-formulated recombinant phage endolysin, SAL-1. Int J Antimicrob Agents. 2013;41(2):156–161. .
   PubMed Web of Science ®Google Scholar
• Jun SY, Jang IJ, Yoon S, et al. Pharmacokinetics and tolerance of the phage endolysin-based candidate drug SAL200 after a single intravenous administration among healthy volunteers. Antimicrob Agents Chemother. 2017;61(6). DOI:10.1128/AAC.02629-16.
   PubMed Web of Science ®Google Scholar
• Yu XQ, Robbie GJ, Wu Y, et al. Safety, tolerability, and pharmacokinetics of MEDI4893, an investigational, extended-half-life, anti-Staphylococcus aureus alpha-toxin human monoclonal antibody, in healthy adults. Antimicrob Agents Chemother. 2017;61(1). DOI:10.1128/AAC.01020-16.
   Web of Science ®Google Scholar
• COMBACTE-NET. Saatellite. [cited 2019 Oct 22]. Available from: https://www.combacte.com/trials/saatellite/#.
   Google Scholar
• Diep BA, Hilliard JJ, Le VT, et al. Targeting alpha toxin to mitigate its lethal toxicity in ferret and rabbit models of Staphylococcus aureus necrotizing pneumonia. Antimicrob Agents Chemother. 2017;61(4). DOI:10.1128/AAC.02456-16.
   Web of Science ®Google Scholar
• Diep BA, Le VT, Visram ZC, et al. Improved protection in a rabbit model of community-associated methicillin-resistant Staphylococcus aureus necrotizing pneumonia upon neutralization of leukocidins in addition to alpha-hemolysin. Antimicrob Agents Chemother. 2016;60(10):6333–6340. .
   PubMed Web of Science ®Google Scholar
• Magyarics Z, Leslie F, Bartko J, et al. Randomized, double-blind, placebo-controlled, single-ascending-dose study of the penetration of a monoclonal antibody combination (ASN100) targeting Staphylococcus aureus cytotoxins in the lung epithelial lining fluid of healthy volunteers. Antimicrob Agents Chemother. 2019;63(8). DOI:10.1128/AAC.00350-19.
   PubMed Web of Science ®Google Scholar
• Arsanis,Inc. Arsanis provides update following completion of planned interim analysis of phase 2 clinical trial of ASN100. [2019 Oct 22]. Available from: https://www.globenewswire.com/news-release/2018/06/28/1530829/0/en/Arsanis-Provides-Update-Following-Completion-of-Planned-Interim-Analysis-of-Phase-2-Clinical-Trial-of-ASN100.html.
   Google Scholar
• Varshney AK, Kuzmicheva GA, Lin J, et al. A natural human monoclonal antibody targeting Staphylococcus Protein A protects against Staphylococcus aureus bacteremia. PLoS One. 2018;13(1):e0190537. .
   PubMed Web of Science ®Google Scholar
• XBiotech, Inc. XBiotech announces top-line results for 514G3 antibody therapy in serious staphylococcus aureus infections. [cited 2019 Oct 22]. Available from: http://investors.xbiotech.com/news-releases/news-release-details/xbiotech-announces-top-line-results-514g3-antibody-therapy?ID=2259222&c=253990&p=irol-newsArticle.
   Google Scholar
• Weems JJ Jr., Steinberg JP, Filler S, et al. Phase II, randomized, double-blind, multicenter study comparing the safety and pharmacokinetics of tefibazumab to placebo for treatment of Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2006;50(8):2751–2755. .
   PubMed Web of Science ®Google Scholar
• Francois B, Mercier E, Gonzalez C, et al. Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: first-in-human trial. Intensive Care Med. 2018;44(11):1787–1796. .
   PubMed Web of Science ®Google Scholar
• Jiang L, Lin J, Taggart CC, et al. Nanodelivery strategies for the treatment of multidrug-resistant bacterial infections. J Interdiscip Nanomed. 2018;3(3):111–121. .
   PubMedGoogle Scholar
• Lehar SM, Pillow T, Xu M, et al. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature. 2015;527(7578):323–328. .
   PubMed Web of Science ®Google Scholar
• Deng R, Zhou C, Li D, et al. Preclinical and translational pharmacokinetics of a novel THIOMAB™ antibody-antibiotic conjugate against Staphylococcus aureus. MAbs. 2019;11(6):1162–1174. .
   PubMed Web of Science ®Google Scholar
• Peck M, Rothenberg ME, Deng R, et al. A phase 1, randomized, single-ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of DSTA4637S, an anti-staphylococcus aureus thiomab antibody-antibiotic conjugate, in healthy volunteers. Antimicrob Agents Chemother. 2019;63.
   Web of Science ®Google Scholar
• Bassetti M, Baguneid M, Bouza E, et al. European perspective and update on the management of complicated skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus after more than 10 years of experience with linezolid. Clin Microbiol Infect. 2014;20(Suppl 4):3–18. .
   PubMed Web of Science ®Google Scholar
• Golan Y. Current treatment options for acute skin and skin-structure infections. Clin Infect Dis. 2019;68(Supplement_3):S206–S212. .
   PubMed Web of Science ®Google Scholar
• Bassetti M, Peghin M, Castaldo N, et al. The safety of treatment options for acute bacterial skin and skin structure infections. Expert Opin Drug Saf. 2019;18(8):635–650. .
   PubMed Web of Science ®Google Scholar
• Sader HS, Rhomberg PR, Duncan LR, et al. In vitro activity and potency of the novel oxazolidinone MRX-I tested against contemporary clinical isolates of gram-positive bacteria. Presented at: ASM Microbe 2017, June 1-15, 2017, New Orleans (LA), US.
   Google Scholar
• Adam HJ, Laing NM, King CR, et al. In vitro activity of nemonoxacin, a novel nonfluorinated quinolone, against 2,440 clinical isolates. Antimicrob Agents Chemother. 2009;53(11):4915–4920. .
   PubMed Web of Science ®Google Scholar
• Chen YH, Liu CY, Ko WC, et al. Trends in the susceptibility of methicillin-resistant Staphylococcus aureus to nine antimicrobial agents, including ceftobiprole, nemonoxacin, and tyrothricin: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006-2010. Eur J Clin Microbiol Infect Dis. 2014;33(2):233–239. .
   PubMed Web of Science ®Google Scholar
• Farrell DJ, Liverman LC, Biedenbach DJ, et al. Surveillance of JNJ-Q2 activity tested against Staphylococcus aureus and beta-hemolytic streptococci as a component of the 2010 SENTRY antimicrobial surveillance program. Diagn Microbiol Infect Dis. 2011;71(4):415–420. .
   PubMed Web of Science ®Google Scholar
• Farrell DJ, Liverman LC, Biedenbach DJ, et al. JNJ-Q2, a new fluoroquinolone with potent In Vitro activity against Staphylococcus aureus, including methicillin- and fluoroquinolone-resistant strains. Antimicrob Agents Chemother. 2011;55(7):3631–3634.
   PubMed Web of Science ®Google Scholar
• Farrell DJ, Turner LL, Castanheira M, et al. Activity of JNJ-Q2 against Staphylococcus aureus isolated from patients with acute bacterial skin and skin-structure infection obtained during a Phase 2 clinical trial. Diagn Microbiol Infect Dis. 2012;74(1):73–74.
   PubMed Web of Science ®Google Scholar
• Jacobs MR, Bajaksouzian S, Windau A, et al. In vitro activity of the new quinolone WCK 771 against staphylococci. Antimicrob Agents Chemother. 2004;48(9):3338–3342. .
   PubMed Web of Science ®Google Scholar
• Karlowsky JA, Laing NM, Baudry T, et al. In vitro activity of API-1252, a novel FabI inhibitor, against clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob Agents Chemother. 2007;51(4):1580–1581. .
   PubMed Web of Science ®Google Scholar
• Kwon AR, Min YH, Ryu JM, et al. In vitro and in vivo activities of DW-224a, a novel fluoroquinolone antibiotic agent. J Antimicrob Chemother. 2006;58(3):684–688. .
   PubMed Web of Science ®Google Scholar
• Lauderdale TL, Shiau YR, Lai JF, et al. Comparative in vitro activities of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, and other quinolones against clinical isolates. Antimicrob Agents Chemother. 2010;54(3):1338–1342. .
   PubMed Web of Science ®Google Scholar
• Lawrence L, Danese P, DeVito J, et al. In vitro activities of the Rx-01 oxazolidinones against hospital and community pathogens. Antimicrob Agents Chemother. 2008;52(5):1653–1662. .
   PubMed Web of Science ®Google Scholar
• Li Z, Liu Y, Wang R, et al. Antibacterial activities of nemonoxacin against clinical isolates of Staphylococcus aureus: an in vitro comparison with three fluoroquinolones. World J Microbiol Biotechnol. 2014;30(11):2927–2932.
   PubMed Web of Science ®Google Scholar
• Paukner S, Gelone SP, Arends SJR, et al. Antibacterial activity of lefamulin against pathogens most commonly causing community-acquired bacterial pneumonia: SENTRY antimicrobial surveillance program (2015–2016). Antimicrob Agents Chemother. 2019;63(4). DOI:10.1128/AAC.02161-18.
   Web of Science ®Google Scholar
• Paukner S, Sader HS, Ivezic-Schoenfeld Z, et al. Antimicrobial activity of the pleuromutilin antibiotic BC-3781 against bacterial pathogens isolated in the SENTRY antimicrobial surveillance program in 2010. Antimicrob Agents Chemother. 2013;57(9):4489–4495.
   PubMed Web of Science ®Google Scholar
• Robertson GT, Bonventre EJ, Doyle TB, et al. In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: microbiology profiling studies with staphylococci and streptococci. Antimicrob Agents Chemother. 2008;52(7):2324–2334. .
   PubMed Web of Science ®Google Scholar
• Scangarella-Oman NE, Ingraham KA, Tiffany CA, et al. In Vitro activity and microbiological efficacy of gepotidacin from a phase 2, randomized, multicenter, dose-ranging study in patients with acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2019;64(3). DOI:10.1128/AAC.01302-19.
   Web of Science ®Google Scholar
• Watson A, Oh JT, Sauve K, et al. Antimicrobial activity of exebacase (Lysin CF-301) against the most common causes of infective endocarditis. Antimicrob Agents Chemother. 2019;63(10). DOI:10.1128/AAC.01078-19.
   Web of Science ®Google Scholar
• Wu J, Wu H, Wang Y, et al. Tolerability and pharmacokinetics of contezolid at therapeutic and supratherapeutic doses in healthy chinese subjects, and assessment of contezolid dosing regimens based on pharmacokinetic/pharmacodynamic analysis. Clin Ther. 2019;41(6):1164–1174 e1164. .
   PubMed Web of Science ®Google Scholar
• Jaffa RK, Pillinger KE, Roshdy D, et al. Novel developments in the treatment of acute bacterial skin and skin structure infections. Expert Opin Pharmacother. 2019;20(12):1493–1502. .
   PubMed Web of Science ®Google Scholar
• Appalaraju B, Baveja S, Baliga S, et al. In vitro activity of a novel antibacterial agent, levonadifloxacin, against clinical isolates collected in a prospective, multicentre surveillance study in India during 2016-18. J Antimicrob Chemother. 2020;75(3):600–608. .
   PubMed Web of Science ®Google Scholar
• Macia-Rodriguez C, Alende-Castro V, Vazquez-Ledo L, et al. Skin and soft-tissue infections: factors associated with mortality and re-admissions. Enferm Infecc Microbiol Clin. 2017;35(2):76–81. .
   PubMed Web of Science ®Google Scholar
• Raya-Cruz M, Payeras-Cifre A, Ventayol-Aguilo L, et al. Factors associated with readmission and mortality in adult patients with skin and soft tissue infections. Int J Dermatol. 2019;58(8):916–924.
   PubMed Web of Science ®Google Scholar
• Del Bono V, Giacobbe DR. Bloodstream infections in internal medicine. Virulence. 2016;7(3):353–365.
   PubMed Web of Science ®Google Scholar